Molecular Mechanisms and Targeted Intervention Strategies of Calcium Overload in Ischemic Stroke - PubMed
5 hours ago
- #neuroprotection
- #ischemic stroke
- #calcium overload
- Ischemic stroke is a leading cause of global neurological mortality and disability.
- Calcium overload is a pivotal mechanism in neuronal and glial cell death during ischemic stroke.
- Excitotoxicity from excessive glutamate release activates NMDA receptors and voltage-dependent calcium channels, leading to intracellular Ca2+ accumulation.
- Calcium dyshomeostasis triggers mitochondrial dysfunction, endoplasmic reticulum stress, ROS generation, and activation of calcium-dependent enzymes like calpain and phospholipase A2.
- Calcium signaling imbalance is linked to programmed cell death forms such as ferroptosis and necroptosis.
- Research extends to microglia and astrocytes, providing significant mechanistic insights.
- Targeted interventions include calcium channel blockers, NMDA receptor antagonists, mitochondrial calcium homeostasis regulators, and CaM/CaMK inhibitors, but clinical translation remains limited.
- Future research should focus on nuanced calcium signaling regulation, developing selective and low-toxicity drugs, and multi-target treatment strategies combining neuroprotection, anti-inflammation, and tissue repair.